During the past year, a long-range study comparing various immunosuppressive regimens in 122 cardiac allografts has been completed, resulting in much valid information. Also, hyperacute rejection of orthotopic cardiac allografts has been pursued immunologically using the lymphocytotoxic antibody test and immunofluorescent technique. The results indicate many similarities between hyperacute rejection of the heart and kidney. Technical problems in orthotopic allotransplantation of the rabbit heart, and heart and body responses after 2.5 hours of hypothermic circulatory arrest were also studied as a part of the project. In the coming year, we propose to extend these studies as follows: 1) experimental modification of the chronic vascular lesion in attenuated cardiac allografts produced in puppies by azathioprine-prednisolone treatment, with special reference to the effect of a fat-enriched diet, and the effect of sustained hypertension; 2) anoxic 24-hour storage of the heart by flushing out the coronary vessels with a solution approximating the intracellular electrolyte composition; 3) hemodynamic studies of the cardiac transplants using a computer system. Effects of digitaloids, epinephrine, norepinephrine, isoproterenol, fluid overloading, and hemorrhage will be studied in cardiac reimplants with and without established reinnervation, and in cardiac allografts without established reinnervation.